Optical Control of Magnetic Feshbach Resonances by Closed-Channel Electromagnetically Induced Transparency.

We control magnetic Feshbach resonances in an optically trapped mixture of the two lowest hyperfine states of a ^{6}Li Fermi gas, using two optical fields to create a dark state in the closed molecular channel. In the experiments, the narrow Feshbach resonance is tuned by up to 3 G. For the broad resonance, the spontaneous lifetime is increased to 0.4 s at the dark-state resonance, compared to 0.5 ms for single-field tuning. We present a new model of light-induced loss spectra, employing continuum-dressed basis states, which agrees in shape and magnitude with loss measurements for both broad and narrow resonances. Using this model, we predict the trade-off between tunability and loss for the broad resonance in ^{6}Li, showing that our two-field method substantially reduces the two-body loss rate compared to single-field methods for the same tuning range.

Shear Viscosity of a Unitary Fermi Gas Near the Superfluid Phase Transition.

We measure the shear viscosity for a resonantly interacting Fermi gas as a function of temperature from nearly the ground state through the superfluid phase transition into the high temperature regime. Further, we demonstrate an iterative method to estimate the local shear viscosity coefficient α(S)(θ) versus reduced temperature θ from the cloud-averaged measurements ⟨α(S)⟩, and compare α(S) to several microscopic theories. We find that α(S) reveals features that were previously hidden in ⟨α(S)⟩.

Observation of conformal symmetry breaking and scale invariance in expanding Fermi gases.

We precisely test scale invariance and examine local thermal equilibrium in the hydrodynamic expansion of a Fermi gas of atoms as a function of interaction strength. After release from an anisotropic optical trap, we observe that a resonantly interacting gas obeys scale-invariant hydrodynamics, where the mean square cloud size = expands ballistically (like a noninteracting gas) and the energy-averaged bulk viscosity is consistent with zero, 0.00(0.04)ℏn, with n the density. In contrast, the aspect ratios of the cloud exhibit anisotropic "elliptic" flow with an energy-dependent shear viscosity. Tuning away from resonance, we observe conformal symmetry breaking, where deviates from ballistic flow.

Anomalous minimum in the shear viscosity of a Fermi gas.

We measure the static shear viscosity η in a two-component Fermi gas near a broad collisional (Feshbach) resonance, as a function of interaction strength and energy. We find that η has both a quadratic and a linear dependence on the interaction strength 1/(k(FI)a), where a is the s-wave scattering length and k(FI) is the Fermi wave vector for an ideal gas at the trap center. For energies above the superfluid transition, the minimum in η as a function of interaction strength is significantly shifted toward the BEC side of resonance, to 1/(k(FI)a)≃0.25.

Observation of shock waves in a strongly interacting Fermi gas.

We study collisions between two strongly interacting atomic Fermi gas clouds. We observe exotic nonlinear hydrodynamic behavior, distinguished by the formation of a very sharp and stable density peak as the clouds collide and subsequent evolution into a boxlike shape. We model the nonlinear dynamics of these collisions by using quasi-1D hydrodynamic equations. Our simulations of the time-dependent density profiles agree very well with the data and provide clear evidence of shock wave formation in this universal quantum hydrodynamic system.

Instrumental control of cardioacceleration induced by central electrical stimulation.

Each of four monkeys (Macaca mulatta) was operantly conditioned to slow and to speed heart rate through a shock-avoidance procedure. During these sessions, electrical brain stimulation that produced tachycardia and pressor responses was delivered on alternate, 64-second segments to one of several brain regions. All animals were able to attenuate the increases in heart rate produced by brain stimulation during the slowing sessions when posterior hypothalamic and striatal regions were stimulated but not when anterior hypothalamic or subthalamic areas were stimulated. During speeding or control sessions during which heart rate was monitored, brain stimulation continued to increase heart rate.

Dietary restriction retards the age-associated loss of rat striatal dopaminergic receptors.

In male Wistar rats subjected to dietary restriction by alternate days of feeding and fasting the normal age-associated loss of striatal dopamine receptors in the brain was substantially retarded. The mean survival time of the rats on the restricted diet was increased by approximately 40 percent compared to control rats given free access to food. Dopamine receptor concentrations in striata of 24-month-old rats that had been on a restricted diet since weaning were 50 percent higher than those of control animals of the same age, and essentially comparable to 3- and 6-month-old control rats.

Dopamine and Abeta-induced stress signaling and decrements in Ca2+ buffering in primary neonatal hippocampal cells are antagonized by blueberry extract.

We have shown previously that dietary blueberry (BB) extract supplementation (S) reversed several parameters of neuronal and behavioral (e.g., cognition) aging in rodents. Additionally, findings indicate that COS-7 cells transfected with muscarinic receptor subtypes (e.g., M1) showed decrements in Ca;{2+} clearance following depolarization (Ca;{2+} Recovery time, Ca;{2+}RT) that were antagonized by BB. Since it has been postulated that at least part of the loss of cognitive function in aging may be dependent upon a dysregulation in calcium homeostasis (i.e., Ca;{2+}RT), we assessed whether: a) Ca;{2+}RT would be altered in dopamine (DA)- or amyloid beta (Abeta)-exposed cultured primary hippocampal neuronal cells (HNC), and b) BB pre-treatment of the cells would prevent these deficits. Thus, control or BB (0.5 mg/ml)-treated HNC were exposed to DA (0.1 mM, 2 hrs), Abeta(40) (25 microM, 24 hrs), Abeta(42) (25 microM, 24 hrs), and Abeta(25-35) (25 microM, 24 hrs), and Ca;{2+}RT following KCl-induced depolarization assessed. Ca;{2+}RT was assessed as the % of HNC showing recovery to 50%-70% of control at 5, 10, or 15 min after depolarization. Results indicated that DA significantly lowered Ca;{2+}RT in the HNC at all time points examined after depolarization. However, BB treatment selectively prevented these declines in Ca;{2+}RT. In the case of Abeta, the greatest effects on Ca;{2+}RT were seen when the hippocampal cells were Abeta(42)-treated. These effects were antagonized by BB treatment. Abeta(40) produced fewer deficits on Ca;{2+}RT than those seen when the HNC were pre-treated with either A;{2+}(42) or A;{2+}(25-35), but BB was relatively ineffective in antagonizing the deficits in Ca;{2+}RT produced by A;{2+}(40) or A;{2+}(25-35). Additional analyses indicated that BBs may be exerting their protective effects in the hippocampal cells by altering levels of phosphorylated MAPK, PKCgamma, and phosphorylated CREB. Therefore it appears that at least part of the protective effect of BBs may involve alterations in stress signaling.

The effects of antioxidants in the senescent auditory cortex.

We investigated whether a 2-month dietary supplementation of antioxidants, in the form of blueberry phytochemicals, could reverse or retard the age-related decline in temporal processing speed observed in the aged rat. To this end, extracellular single unit responses to frequency modulated (FM) sweeps were recorded in the primary auditory cortex (AI) of aged rats that had been placed on either a blueberry-supplemented or control diet 2 months prior to the physiological recordings. Results showed that most cells recorded from the blueberry-fed rats responded most vigorously to fast FM sweeps, similar to that observed in young rats. In contrast, the majority of cells recorded from the control rats showed a preference for slow FM sweep rates. These results suggest that age-related changes in temporal processing speed in A1 may be reversed by dietary supplementation of blueberry phytochemicals.

Membrane alterations as causes of impaired signal transduction in Alzheimer's disease and aging.

Changes in cell-membrane composition in normal aging and in Alzheimer's and other age-related diseases appear to result in impaired neurotransmitter-triggered signal transduction. The impaired signal transduction seems to be related to dysfunctions in the coupling of G proteins to their receptors and effectors. Direct demonstration of altered physiochemical properties of brain tissue of patients with Alzheimer's disease has been achieved by small-angle X-ray diffraction. In this disease, thinner membranes correlate with a 30% decrease in moles of cholesterol:phospholipid. Such changes can affect directly the coupling and uncoupling properties of G proteins, and can account for signal transduction deficits. These findings offer a complementary alternative to the beta-amyloid hypothesis, and an opportunity to consider new types of therapeutic interventions.

Blueberry extract alters oxidative stress-mediated signaling in COS-7 cells transfected with selectively vulnerable muscarinic receptor subtypes.

Previous research has indicated that selective vulnerability to oxidative stress may be important in determining regional differences in functional declines in neuronal aging. Oxidative stress vulnerability may involve selective deficits in Ca2+ buffering (Ca2+ recovery time following oxotremorine application) to oxidative stress, determined in-part by receptor subtype with M1, M2 and M4 AChR showing greater oxidative stress-induced loss [via dopamine (DA) exposure for 4 hrs] of Ca2+ recovery time than that seen in M3 or M5 cells. Deficits were antagonized by pre-treating M1, M2, or M4 AChR-transfected cells with blueberry (BB) extract. Thus, we assessed whether these differences in oxidative stress vulnerability might involve differential patterns of DA-induced protein kinase (PKCalpha, PKCgamma) and/or cyclic AMP response element binding protein (CREB) activation, and whether these differences might be altered by BB treatment. M1 or M3 AChR-transfected COS-7 cells were exposed to 1 mM DA, and activation of phospho-(p) mitogen-activated protein kinase (MAPK) signaling was examined by immunoblotting analyses. The results showed that DA increased pCREB and pPKCgamma for both M1- and M3-transfected cells, and BBs decreased these DA-induced alterations, when measured by immunoblotting techniques. Taken together these findings suggest that M1/M3 oxidative stress sensitivity differences may involve differential signaling in pMAPK and pCREB under oxidative stress conditions, suggesting that the native protection in these receptors against oxidative stress and inflammation may be derived from reduced activation. These findings also suggest that BB may antagonize oxidative stress effects induced by DA in M1-transfected cells by lowering activation of pCREB, and possibly pPKCgamma.

Dopamine-induced stress signaling in COS-7 cells transfected with selectively vulnerable muscarinic receptor subtypes is partially mediated via the i3 loop and antagonized by blueberry extract.

Muscarinic receptors (MAChRs) are intimately involved in various aspects of both neuronal and vascular functioning, and there is selective oxidative stress sensitivity (OSS) among MAChR subtypes, with M1, M2, and M4 showing>OSS. OSS was assessed by determining the loss of ability of the cell to extrude or sequester Ca2+ following oxotremorine-induced depolarization following exposure to dopamine (DA) subtypes in transfected COS-7 cells. This OSS can be prevented by pretreatment with blueberry (BB) extract. Present studies were carried out to determine BB treatment of the cells transfected with wild type, truncated or chimeric [where the i3 loop of one receptor was switched with the i3 loop of the other; i.e., M1(M3i3) and M3(M1i3)] receptors would alter DA-induced changes in calcium buffering and would confer protection through alterations in pMAPK, pCREB or PKC signaling. These findings also suggest that BB may antagonize OS effects by lowering activation of pCREB and possibly PKCgamma induced by DA. In the truncated and chimeric receptors, results indicated that BB reduced OSS in response to DA in M1-transfected cells. However, BBs were also effective in preventing these Ca2+ buffering deficits in cells transfected with M1 receptors in which the i3 loop had been removed, but only partially enhanced the protective effects of the M3 i3 loop in the M1(M3i3) chimerics. A similar partial effect of BBs was seen in the M3(M1i3) chimerics which showed increased OSS in response to DA. It appears that antioxidants found in BBs might be targeting additional sites on these chimerics to decrease OSS.

Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation.

Ample research indicates that age-related neuronal-behavioral decrements are the result of oxidative stress that may be ameliorated by antioxidants. Our previous study had shown that rats given dietary supplements of fruit and vegetable extracts with high antioxidant activity for 8 months beginning at 6 months of age retarded age-related declines in neuronal and cognitive function. The present study showed that such supplements (strawberry, spinach, or blueberry at 14.8, 9.1, or 18.6 gm of dried aqueous extract per kilogram of diet, respectively) fed for 8 weeks to 19-month-old Fischer 344 rats were also effective in reversing age-related deficits in several neuronal and behavioral parameters including: oxotremorine enhancement of K(+)-evoked release of dopamine from striatal slices, carbachol-stimulated GTPase activity, striatal Ca(45) buffering in striatal synaptosomes, motor behavioral performance on the rod walking and accelerod tasks, and Morris water maze performance. These findings suggest that, in addition to their known beneficial effects on cancer and heart disease, phytochemicals present in antioxidant-rich foods may be beneficial in reversing the course of neuronal and behavioral aging.

Polyphenolics enhance red blood cell resistance to oxidative stress: in vitro and in vivo.

In this study we investigated the potential antioxidant properties of blueberry polyphenolics in vitro and vivo, using red blood cell (RBC) resistance to reactive oxygen species (ROS) as the model. In vitro incubation with anthocyanins or hydroxycinnamic acids (HCA) (0.5 and 0.05 mg/ml) was found to enhance significantly RBC resistance to H2O2 (100 microM) induced ROS production. This protection was also observed in vivo following oral supplementation to rats at 100 mg/ml. However, only anthocyanins were found to afford protection at a significant level, this at 6 and 24 h post supplementation. This protection was not consistent with the measured plasma levels of anthocyanins. Indeed, plasma polyphenolic concentrations were highest after 1 h, declining considerably after 6 h and not detected after 24 h. The difference in absorption between anthocyanins and HCA is likely to have contributed to the observed difference in their abilities to afford protection to RBC. This protection represents a positive role following dietary consumption of polyphenolics from blueberries, against ROS formation within RBC in vivo.

Reduction of motor behavioral deficits in senescent animals via chronic prolactin administration. II. Non-stereotypic behaviors.

The effects of chronic prolactin administration on three non-stereotypic psychomotor behaviors (inclined screen performance, rod walking and wire hanging) were examined in senescent (24 month) Fisher 344 rats. Prolactin (150 ng/hr) was administered for 7 days via Alzet minipumps to rats which had been pretested on the three tasks. The animals were tested on days 4 and 7 following the implants and the pumps were removed after testing on day 7. In order to assess the persistence of any prolactin effects on psychomotor performance the animals were tested again on days 7 and 14 after pump removal. Control animals were implanted with Alzet pumps containing only saline and tested in a similar manner. Results demonstrated that the prolactin treated animals showed improvements on both the inclined screen and rod walking tasks but not the wire hanging test. Moreover, the improved performance seen on the inclined screen test persisted for as long as 7 days after pump removal. Results are discussed in terms of the importance of techniques which increase striatal dopaminergic responsivity on enhancing psychomotor performance in senescence.

Muscarinic receptor concentrations and dopamine release in aged rat striata.

The extent to which age-related decreases in muscarinic enhancement of K(+)-evoked dopamine release (K(+)-ERDA) from perifused striatal slices is dependent upon the loss of striatal muscarinic receptors (mAChR) was determined. Both K(+)-ERDA and mAChR (M1, M2) concentrations were assessed from the same animals (3, 5-7 and 24-27 months). Results indicated associated decreases of 70% in oxotremorine-enhanced K(+)-ERDA and 36% in Bmax (3H-QNB) (3 and 24-27 months groups). Decrease of mAChR Bmax was not the result of membrane sequestration. Although both the concentrations of M1 and M2 muscarinic receptor subtypes decline with age, only the M2 receptor decline was correlated with the age-related decreases in muscarinic enhancement of K(+)-ERDA (r = .71, p less than 0.001). Results suggest that age-related decreases in mAChR concentrations as being partially responsible for deficits in muscarinic enhancement of K(+)-evoked release of DA.

Effect of age on sensitivity to pain and brain opiate receptors.

Age-related differences in sensitivity to pain as induced by heat and electrical shock were seen among groups of rats; 2-3, 6-12, and 24 months of age. These are differences were at least partially obliterated by naloxone treatment, suggesting that changes may occur in the endogenous opioid system during aging. In contrast to higher pain thresholds in older animals, however, are decreased concentrations of opiate receptors in the frontal poles, striatum and hippocampus. Anterior cortex and amygdala exhibit a trend toward decreased concentration with increased age, but this is not significant. No age changes in binding affinity occur in any of the brain regions examined. Possible explanations for the apparent discrepancy between altered receptors and response include: higher endogenous opioid levels in aged rats, mediation of pain sensitivity by brain regions other than those examined, difficulties inherent in attempting to localize age changes at a single step in such a complex process, and possibly differential spinal pathways mediating the various types of pain.

Reduction of motor behavioral deficits in senescent animals via chronic prolactin administration. I. Rotational behavior.

The effects of chronic prolactin administration on amphetamine or dopamine (DA) induced rotational behavior was examined in mature (6 month) and senescent (24 month) Wistar rats which were unilaterally lesioned in the left substantia nigra with 6-hydroxydopamine. Prolactin (150 ng/hr) was administered for 7 days via subcutaneously implanted Alzet minipumps. Amphetamine (AMPH) (0, 10 micrograms) or DA (0, 25 micrograms) was administered through cannula which had been implanted into the right (intact) striatum. Both DA-active agents were given prior to pump implantation and on day 4 of prolactin administration. The AMPH was dissolved in saline (1 microliter; pH, 5.5-6.0), while DA was dissolved in N2 bubbled distilled H2O (1 microliter; pH, 5.5-6.0) and the animals were pretreated with nialamide (50 mg/kg) intraperitoneally 1 hr before DA or DA-vehicle injection. The order of drug administration was counterbalanced within the age groups. Results showed that both groups of animals exhibited higher rotational behavior scores following prolactin treatment. In fact, there was a trend toward greater enhancement of rotational behavior in the senescent animals following prolactin treatment than that seen in mature animals. These results parallel those reported previously wherein it was found that striatal DA receptor concentrations (as assessed with [3H]spiperone binding) were higher in prolactin treated mature and senescent animals than in their respective controls. The findings suggest that there is a relationship between increases in the density of striatal DA receptors and improvement in motor performance tasks in senescent animals.